Prostate cancer cells preferentially home to osteoblast-rich areas in the early stages of bone metastasis: evidence from in vivo models.
Reeves, Kimberley J
AffiliationThe Mellanby Centre for Bone Research, Department of Human Metabolism, The University of Sheffield, Sheffield, UK
MetadataShow full item record
AbstractIt has been suggested that metastasis-initiating cells gain a foothold in bone by homing to a metastastatic microenvironment (or "niche"). Whereas the precise nature of this niche remains to be established, it is likely to contain bone cell populations including osteoblasts and osteoclasts. In the mouse tibia, the distribution of osteoblasts on endocortical bone surfaces is non-uniform, and we hypothesize that studying co-localization of individual tumor cells with resident cell populations will reveal the identity of critical cellular components of the niche. In this study, we have mapped the distribution of three human prostate cancer cell lines (PC3-NW1, LN-CaP, and C4 2B4) colonizing the tibiae of athymic mice following intracardiac injection and evaluated their interaction with potential metastatic niches. Prostate cancer cells labeled with the fluorescent cell membrane dye (Vybrant DiD) were found by two-photon microscopy to be engrafted in the tibiae in close proximity (∼40 µm) to bone surfaces and 70% more cancer cells were detected in the lateral compared to the medial endocortical bone regions. This was associated with a 5-fold higher number of osteoblasts and 7-fold higher bone formation rate on the lateral endocortical bone surface compared to the medial side. By disrupting cellular interactions mediated by the chemokine (C-X-C motif) receptor 4 (CXCR4)/chemokine ligand 12 (CXCL12) axis with the CXCR4 inhibitor AMD3100, the preferential homing pattern of prostate cancer cells to osteoblast-rich bone surfaces was disrupted. In this study, we map the location of prostate cancer cells that home to endocortical regions in bone and our data demonstrate that homing of prostate cancer cells is associated with the presence and activity of osteoblast lineage cells, and suggest that therapies targeting osteoblast niches should be considered to prevent development of incurable prostate cancer bone metastases. © 2014 American Society for Bone and Mineral Research.
CitationProstate cancer cells preferentially home to osteoblast-rich areas in the early stages of bone metastasis: evidence from in vivo models. 2014, 29 (12):2688-96 J Bone Miner Res
JournalJournal of Bone and Mineral Research
- Modifying the osteoblastic niche with zoledronic acid in vivo-potential implications for breast cancer bone metastasis.
- Authors: Haider MT, Holen I, Dear TN, Hunter K, Brown HK
- Issue date: 2014 Sep
- Abrogation of prostaglandin E-EP4 signaling in osteoblasts prevents the bone destruction induced by human prostate cancer metastases.
- Authors: Watanabe K, Tominari T, Hirata M, Matsumoto C, Maruyama T, Murphy G, Nagase H, Miyaura C, Inada M
- Issue date: 2016 Sep 9
- Pharmacological targeting of CXCL12/CXCR4 signaling in prostate cancer bone metastasis.
- Authors: Conley-LaComb MK, Semaan L, Singareddy R, Li Y, Heath EI, Kim S, Cher ML, Chinni SR
- Issue date: 2016 Nov 3
- Skeletal localization and neutralization of the SDF-1(CXCL12)/CXCR4 axis blocks prostate cancer metastasis and growth in osseous sites in vivo.
- Authors: Sun YX, Schneider A, Jung Y, Wang J, Dai J, Wang J, Cook K, Osman NI, Koh-Paige AJ, Shim H, Pienta KJ, Keller ET, McCauley LK, Taichman RS
- Issue date: 2005 Feb
- Establishing human prostate cancer cell xenografts in bone: induction of osteoblastic reaction by prostate-specific antigen-producing tumors in athymic and SCID/bg mice using LNCaP and lineage-derived metastatic sublines.
- Authors: Wu TT, Sikes RA, Cui Q, Thalmann GN, Kao C, Murphy CF, Yang H, Zhau HE, Balian G, Chung LW
- Issue date: 1998 Sep 11